Synthesis and evaluation of 6-(11C-methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein by PET

Qingzhen Yu; Katsushi Kumata; Hua Li; Yiding Zhang; Zhen Chen; Xiaofei Zhang; Tuo Shao; Akiko Hatori; Tomoteru Yamasaki; Lin Xie; Kuan Hu; Gangqiang Wang; Lee Josephson; Shaofa Sun; Ming-Rong Zhang; Steven H Liang

doi:10.1016/j.bmcl.2019.126879

Synthesis and evaluation of 6-(¹¹C-methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein by PET

Bioorg Med Chem Lett. 2020 Feb 15;30(4):126879. doi: 10.1016/j.bmcl.2019.126879. Epub 2019 Dec 17.

Authors

Affiliations

¹ Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States.
² Department of Radiopharmaceutics Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.
³ Hubei Collaborative Innovation Centre for Non-power Nuclear Technology, College of Nuclear Technology & Chemistry and Biology, Hubei University of Science and Technology, Xianning 437100, PR China.
⁴ Hubei Collaborative Innovation Centre for Non-power Nuclear Technology, College of Nuclear Technology & Chemistry and Biology, Hubei University of Science and Technology, Xianning 437100, PR China. Electronic address: sunshaofa@hbust.edu.cn.
⁵ Department of Radiopharmaceutics Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan. Electronic address: zhang.ming-rong@qst.go.jp.
⁶ Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States. Electronic address: liang.steven@mgh.harvard.edu.

Abstract

Transmembrane AMPA receptor regulatory proteins (TARPs) are a recently discovered family of proteins that modulate AMPA receptors activity. Based on a potent and selective TARP subtype γ-8 antagonist, 6-(methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one (compound 9), we perform the radiosynthesis of its ¹¹C-isotopologue 1 and conduct preliminary PET evaluation to test the feasibility of imaging TARP γ-8 dependent receptors in vivo.

Keywords: AMPA; Carbon-11; Positron emission tomography; TARP; Transmembrane AMPA receptor regulatory proteins.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzoxazoles / chemical synthesis
Benzoxazoles / chemistry*
Brain / diagnostic imaging*
Carbon Radioisotopes / chemistry
Feasibility Studies
Isotope Labeling
Positron-Emission Tomography*
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / chemistry
Rats
Receptors, AMPA / metabolism*

Substances

Benzoxazoles
Carbon Radioisotopes
Carbon-11
Radiopharmaceuticals
Receptors, AMPA
benzo(d)oxazol-2(3H)-one

Grants and funding

R01 MH120197/MH/NIMH NIH HHS/United States